Using skeletal muscle as a non-chondrogenic source tissue, it has been shown that this differentiated tissue retains the capacity to alter its mode of differentiation and transform into hyaline cartilage when grown on demineralized bone (bone Matrix). This same tissue regenerates skeletal muscle when grown, as control, on gels of Type I collagen. Biochemical studies suggest that skeletal muscle holds the synthesis of cartilage-type molecules in abeyance and that the environment (i.e. bone matrix) elicits their production. The experimental system is thus useful to investigate the control of skeletal muscle differentiation. Such studies are applicable to development, as well as the biochemical basis of diseases such as muscular dystrophy, arthritis, and various metabolic disorders of muscle and cartilage. The specific aim of the proposed studies is to examine the synthesis of muscle-specific proteins and determine whether a differentiated cell type can express characteristics of more than one phenotype at the same time, and if not, in what form are these syntheses maintained? The proposed methods include: 1) a biochemical characterization of actin, myosin, creatine phosphokinase, acetylcholinesterase, and acetylcholine receptor synthesis during the transformation. These experiments will determine whether skeletal muscle can remain functionally intact in the face of a chondrogenic stimulus and whether the possible disappearance of actin and myosin synthesis is linked to the disappearance of other specific biosyntheses. The experiments also include: 1) cell-free translation of mRNA from transforming cultures to determine whether control of the synthesis of the above proteins lies at the transcriptional or translational levels, 2) an investigation of the effect of various nutritional media on muscle-specific protein synthesis, and 3) parallel light and electron microscopic studies to document the morphology of the transforming tissue and to specifically localize cells which synthesize acetylcholinesterase and acetylcholine receptor within the population of cells explanted onto bone matrix.